This research proposal is being undertaken to evaluate factors governing lipoprotein metabolism in the normal state and subsequently in association with atherosclerosis in families with lipoprotein abnormalities that are inherited as autosomal dominant traits. The project will involve investigation in several species and is broadly divided into physiologic and pathophysiologic studies. Under physiologic studies, parameters of lipoprotein metabolism in normal human subjects will be established. The less complex lipoproteins of the estradiol-treated rooster will be studied as a simplified animal model. A sub-human primate, the baboon, will be utilized to study simultaneously lipid and protein metabolism. Under pathophysiologic studies, humans with autosomal dominant forms of inherited hyperlipoproteinemia and atherosclerosis will be investigated to localize defects in lipoprotein metabolism. Lipoprotein studies in the estradiol-treated rooster will be performed to determine the influence of a high cholesterol diet on lipoprotein metabolism. The influence of the intestine on lipoprotein metabolism will be investigated in the baboon with ileal diversion or jejunectomy.